The present invention relates to a novel method for preparing benzamides and, more particularly to a method for preparing a class of benzamides (including benzofuran carboxamides) are particularly useful as antiemetic agents for cancer chemotherapy induced emesis because they do not appear to be dopamine antagonists.
U.S. Pat. Nos. 3,177,252 to Thominet and U.S. Pat. 3,342,826 to Miller disclose a number of benzamide derivatives which are useful antiemetic and antipsychotic agents. More recently, European Publication No. 0 147 044 disclosed that benzofuran carboxamides constitute another useful class of antiemetic agents. In addition to exhibiting antiemetic activity, most of these compounds are dopamine antagonists. While the dopaminergic response associated with these compounds can be useful, it can also complicate their administration and limit dosage. This is particularly true when the benzamides are used in high dosages to control the emesis associated with chemotherapy. In this application, the compounds are often accompanied by extrapyramidal side effects.
Recent studies have shown that there is a class of benzamides which are antiemetically effective and which do not exhibit a dopaminergic response. These antiemetics are characterized in that they include a secondary amino group in the amido side chain. A number of these compounds are the subject of related and commonly assigned Application Ser. No. 905,215 filed Sept. 9, 1986, now U.S. Pat. No. 4,772,459, patented 09/20/88. Examples are 5-chloro-N-(2-pyrrolidinylmethyl)-2,3dihydrobenzo-[b]furan-7-carboxamide; 4-amino-5-chloro-N(2-pyrrolidinylmethyl)-2,3-dihydrobenzo[b]furan7-carboxa mide and 4-amino-5-chloro-2-methoxy-N(2-pyrrolidinylmethyl)benzamide.